System and method for single or multiple bead distribution with an adjustable capillary

ABSTRACT

A system for processing a plurality of solid supports comprises a tubular member having a proximal end, a distal end, and a lumen terminating at the distal end. A stop is positioned within the lumen at a location spaced about the distal end and is sized to permit fluids to pass through the lumen while preventing the passage of solid supports. A fluid transfer device is configured to transfer fluids through the lumen such that when a fluid containing one or more solid supports is aspirated into the lumen, a solid support may be drawn into the lumen to lodge against the stop.

BACKGROUND OF THE INVENTION

[0001] This invention relates generally to the handling and processingof solid supports, such as beads. More specifically, the inventionrelates to systems and techniques for placing solid supports into anorganized array.

[0002] In modern chemistry, large libraries of chemical compounds areoften created from which certain compounds which are of interest may beidentified. The creation of such libraries may be accomplished with asynthesizing process where various compounds are placed on solidsupports, such as spherical beads. Such processes are well known withinthe art, and are described in, for example, U.S. Pat. No. 5,503,805, thecomplete disclosure of which is herein incorporated by reference.

[0003] After synthesis, it is often desirable to analyze the compoundssynthesized on the beads. One such process is by placing an assortmentof beads in an assay solution and observing whether a chemical reactionoccurs. For example, groups of beads which include synthesized chemicalsmay initially be placed into a plurality of wells where a portion of thecompound on the beads is photo-chemically released. Assays are thenperformed on each well. For wells producing a positive result, thegroups of beads are then transferred into another well or are furtherdivided and placed into a plurality of wells so that further testing canoccur to identify the compound. Hence, to successfully perform suchassays, the beads need to be transferred to different locations.

[0004] When handling such beads, the beads are usually held within aliquid medium, such as water, to help prevent (among other reasons) thebeads from sticking together. Usually, such beads are very small, e.g.on the order of about 5 μm to 300 μm. As such, transferring of suchsmall beads from one location to another while held within a liquidmedium may be difficult and challenging. Transferring such small beadsis especially challenging when a known quantity of beads, such as asingle bead, must be individually transferred from a group of beads andplaced in a test well. Further, it is often convenient to separate thebeads into arrays that are compatible with automated screening systems.For example, much of the automated equipment now uses standardfootprints, such as 96 well plates, 864 well plates, and the like.

[0005] Exemplary techniques for separating and organizing solid supportsare described in, for example, U.S. Pat. No. 5, 722,470 and U.S. patentapplication Ser. No. 08/637,123, filed Apr. 24, 1996, the completedisclosures of which are herein incorporated by reference. The inventionis related to other techniques for separating solid supports and placingthe solid supports into an organized array. The techniques of theinvention permit the transferring of a single bead, or a known quantityof beads, in a repeatable manner.

SUMMARY OF THE INVENTION

[0006] The invention provides for the transfer of solid supports fromone location to another. One particular feature of the invention is theability to transfer a known quantity of solid supports in a repeatableand efficient manner. In one embodiment, a system for processing aplurality of solid supports comprises a tubular member having a proximalend, a distal end, and a lumen terminating at the distal end. A stop ispositioned with the lumen at a location spaced above the distal end andis sized to permit fluids to pass through the lumen while preventing thepassage of solid supports. A fluid transfer device is provided totransfer fluids through the lumen such that when a fluid containingmultiple solid supports is aspirated into the lumen, one or more solidsupports may be drawn into the lumen until lodging against the stop.Hence, a known quantity of solid supports may be captured within thelumen simply by adjusting the position of the stop relative to thedistal end of the tubular member. Once the solid supports are captured,the tubular member may be transferred to another location and the solidsupports expelled by forcing liquids out of the distal end using thefluid transfer device.

[0007] In one particular aspect, the fluid transfer device comprises asyringe pump and a length of tubing coupling the syringe pump to thetubular member. In this way, the syringe pump may be operated toaspirate fluids into the tubular member to capture one or more solidsupports into the lumen, and to irrigate fluids from the tubular memberto expel any captured solid supports. Conveniently, a source of fluidmay be coupled to the syringe pump.

[0008] In another particular aspect, the stop comprises a wire that isslidable within the lumen to permit the spacing between the distal endof the wire and the distal end of the tubular member to be adjusted. Inthis way, the number of potential solid supports that may be capturedwithin a lumen may easily be adjusted.

[0009] In still another aspect, a reservoir is provided having aplurality of solid supports. A moving mechanism is also provided to movethe tubular member relative to the reservoir to permit placement of thedistal end of the tubular member into the reservoir. The system may alsoinclude a plate having a plurality of wells, and the moving mechanismmay be configured to move the tubular member relative to the plate topermit any solid supports to be expelled from the tubular member andinto the wells of the plate. In one particular aspect, the movingmechanism comprises a movable arm to move the tubular member along the Zaxis, and a movable stage onto which the reservoir and the plate areheld. The stage is movable along the X and Y axes so that the plate maybe appropriately positioned relative to the tubular member.Conveniently, a controller may be provided to control operation of thefluid transfer device and the moving mechanism.

[0010] Advantageously, the system may include a plurality of tubularmembers that each have a lumen and a stop disposed within the lumen in amanner similar to that just described. A manifold may be coupled to eachof the tubular members, with the fluid transfer device being coupled tothe manifold. In this way, the throughput of the system may be greatlyincreased by introducing the tubular members into an array of reservoirsso that each tubular member may capture one or more solid supports.

[0011] In another particular aspect, the lumen may have a diameter inthe range from about 190 μm to about 210 μm, and the solid supports mayhave a mean diameter in the range from about 120 μm to about 140 μm.Further, the wire may have an outer diameter in the range from about 125μm to about 150 μm to permit fluids to pass between the wire and thetubular member when aspirating and irrigating fluids. However, it willbe appreciated that other sizes may be used. For example, in some casesthe lumen may have a diameter in the range from about 100 μm to about250 μm.

[0012] The invention further provides an exemplary method for processingsolid supports having at least one chemical that is synthesized onto thesolid supports. According to the method, a tubular member is providedhaving a proximal end, a distal end, and a lumen terminating at thedistal end. A stop is positioned within the lumen at a location spacedabove the distal end. The distal end of the tubular member is placedinto a fluid having a plurality of solid support, and at least some ofthe fluid is aspirated into the lumen. The aspirated fluid travels pastthe stop to draw at least one of the solid supports into the lumen untillodging against the stop. The liquid may be aspirated for a timesufficient to permit the space between the stop and the distal end to befilled with a linear array of solid supports. For example, the tubularmember may be employed to capture about one to about 10 solid supportswithin the lumen, although in some cases larger amounts may be captured.

[0013] After the solid supports have been captured within the lumen, thetubular member may be removed from the liquid and transferred to anotherlocation. Fluid may then be forced through the lumen and past the stopto expel the solid supports from the tubular member. Conveniently, thefluid and the solid supports may be held within a reservoir, and thetubular member may be moved relative to the reservoir to place thedistal end into the fluid. After removing the tubular member from thereservoir, the tubular member may be moved over a multi-well plate topermit the solid supports to be expelled into one of the wells of theplate.

[0014] In another aspect, the lumen may be primed with a fluid to removesubstantially all gas bubbles from the lumen prior to aspirating thefluid. In another aspect, multiple tubular members may be provided thateach have a lumen and a stop within the lumen. In this way, a distal endof each of the tubular members may be simultaneously introduced into thefluid, and fluid aspirated into each of the lumens to draw at least onesolid support into each of the lumens.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015]FIG. 1 is a schematic diagram of a system for processing solidsupports according to the invention.

[0016]FIG. 2 is a schematic diagram of an alternative system forprocessing solid supports according to the invention.

[0017]FIG. 3 is a more detailed view of an array of tubular membersemployed to capture and transfer solid supports.

[0018]FIG. 4 is a front perspective view of one exemplary embodiment ofa multi-channel capillary manifold that may be employed tosimultaneously process multiple solid supports according to theinvention.

[0019]FIG. 5 is a front view of the manifold of FIG. 4.

[0020]FIG. 5A is a cross-sectional side view of the manifold of FIG. 5taken along lines A-A.

[0021]FIG. 5B is a more detailed view of a tubular member of section Bof the manifold of FIG. 5A.

[0022]FIG. 5C is a more detailed view of a wire of section C of FIG. 5A.

[0023]FIG. 6 is an exploded view of the capillary manifold of FIG. 5A.

[0024]FIG. 7 is a flow chart illustrating one method for processingsolid supports according to the invention.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

[0025] The invention provides techniques for transferring a knownquantity of solid supports in a repeatable manner. The techniques may beused to transfer a single solid support or a group of known size. Forexample, the techniques may be employed to transfer a group that is therange from about 2 to about 10 solid supports in a repeatable manner sothat each time a group is transferred, it will contain the same numberof solid supports.

[0026] In one aspect, the solid supports processed by the invention maycomprise small beads onto which chemical compounds have beensynthesized. Such beads are typically small, usually being on the orderof about 5 μm to about 300 μm in diameter, and more usually from about80 μm to about 200 μm. The chemicals may be synthesized onto the solidsupports using any one of a variety of techniques as is known in theart, including those described in U.S. Pat. No. 5,503,805, previouslyincorporated by reference. Such beads may conveniently be constructed ofa polymer, such as a polystyrene and polyethylene glycol, and aregenerally sperical in geometry. Such beads are available from a varietyof commercial suppliers, including, for example, Nova BioChem.

[0027] One use of the invention is to facilitate screening of thechemical compounds following synthesis. For example, followingsynthesis, the beads may be placed into one or more common storagelocations or reservoirs and stored in a random manner. The invention maybe utilized to systematically transfer one or more beads from thereservoir or reservoirs to permit them to be placed into the wells of amultiwell plate where the solid supports may be screened using commonscreening equipment and techniques. For example, once the beads havebeen transferred into the wells of the plate, at least some of thecompounds may be released from the solid support so that assays may beperformed on the released compounds. The assay results may then bemeasured and certain solid supports may be chosen for decoding in orderto identify or further evaluate the compounds. To facilitate thisprocess, the invention may be used to remove the beads from the wells ofthe multiwell plate for transfer to another location, such as to thewells of another multi-well plate.

[0028] The invention facilitates the processing of solid supports withthe use of a tubular member having an internal lumen. A stop is placedwithin the lumen at a location that is spaced apart from the distal endof the tubular member. The stop is configured so that liquids may beaspirated or irrigated through the lumen around the stop. In this way,the tubular member may be placed into a reservoir containing a liquidand solid supports, and liquid aspirated into the lumen until one ormore solid supports are drawn into the lumen and engage the stop. Thetubular member may then be removed from the reservoir and transferred toanother location where a liquid may be forced through the lumen to expelthe solid support. Although the invention may utilize a single tubularmember, in some cases it may be desirable to include an array ormanifold of tubular members to permit the parallel transfer of multiplesolid supports or multiple groups of solid supports.

[0029] Referring now to FIG. 1, a system 10 for processing solidsupports will be described. System 10 comprises a capillary tubeassembly 12 that is constructed of a capillary tube 14 having a proximalend 16, a distal end 18, and a central lumen 20 extending betweenproximal end 16 and distal end 18. Conveniently, tube 14 may beconstructed of a polyimide tubing, commercially available fromCole-Parmer. Positioned within lumen 20, is a wire 22 having a distalend 24 that is spaced apart from distal end 18 of capillary tube 14.Such a spacing may be varied depending upon the number of beads 26 thatare to be captured within lumen 20 as described hereinafter. Wire 22 hasan outer diameter that is smaller than the inner diameter of capillarytube 14 to permit liquids to flow through lumen 20 when capturing orexpelling the beads.

[0030] Coupled to proximal end 16 is a connector 28 to provide a fluidconnection between capillary tube 14 and a syringe pump 30 via a line32. Syringe pump 30 comprises a housing 34 that includes a syringemechanism 36 and a valve structure 38. Valve structure 38 includes aconnector 40 to facilitate coupling of line 32 to syringe pump 30. Valvestructure 38 also includes a connector 42 to permit a liquid supply 44to be coupled to syringe pump 30 via a line 46. Valve structure 38 isconfigured so that when syringe mechanism 36 is extended, liquid fromsupply 44 is drawn through line 46 and into syringe mechanism 36. Whensyringe mechanism 36 is compressed, the captured liquid is forced out ofconnector 40 and through line 32 where it flows through capillary tube14. One example of such a syringe pump that is configured to operate inthis manner is a XL 3000 Modular Digital syringe pump, commerciallyavailable from Cavro Scientific Instruments, Inc. However, it will beappreciated that other types of syringe pumps, as well as other types offluid transfer systems may be employed to irrigate liquids through lumen20 as well as to aspirate fluids into lumen 20.

[0031] System 10 further includes a reservoir 48 containing a supply ofbeads 26 which are held within a liquid 50. Beads 26 are generallyspherical in geometry and may include synthesized chemicals that form acombinatorial library of chemical compounds as previously described. Thetypes of liquid in which beads 26 may be stored include liquids such aswater, 50% ethanol in water, and the like. Typically, the liquid withinsupply 44 will comprise the same type of liquid held in reservoir 48.System 10 also includes a plate 52 having a plurality of wells 54 forreceiving one or more beads that have been transferred from reservoir48. Conveniently, plate 52 may be constructed to have a standardfootprint so that it may be useful with standardized equipment whenscreening the chemical compounds, as well as for other processes as isknown in the art.

[0032] In one method of operation, beads are transferred from reservoir48 to wells 54 by first operating syringe pump 30 to fill syringemechanism 36 with liquid from supply 44. In this way, line 56 iscompletely filled with liquid. Syringe pump 30 is then operated to forceliquid through line 32, thereby priming line 32 and filling lumen 20.Preferably, syringe pump 30 is operated until lumen 20 is substantiallycompletely filled with liquid to remove any gas bubbles. Capillary tube14 may then be inserted into reservoir 48 and syringe pump 30 may againbe operated to irrigate a small amount of fluid through lumen 20 toensure that no gas bubbles exist within lumen 20 as well as tocompensate for the amount of liquid that will be lost when beads 26 areaspirated into capillary tube 14. In some cases, the released liquid mayalso serve to provide a small stirring effect on beads 26 to facilitatetheir capture into lumen 20.

[0033] Syringe pump 30 is then operated to aspirate liquids into lumen20. As liquid from reservoir 48 is aspirated into lumen 20, some ofbeads 26 are drawn into lumen 20 as shown. The number of beads that maybe captured into lumen 20 depends on the distance between distal end 24of wire 22 and distal end 18 of capillary tube 14. As shown, three beadshave been captured in a linear array. However, it will be appreciatedthat other numbers of beads may be captured during a single pickingoperation. For example, wire 22 may be configured so that only a singlebead is captured during each picking step. Alternatively, groups fromabout two to about 10 beads may be captured at a time. Configuration ofcapillary tube assembly 12 is advantageous in that a known quantity ofbeads may be captured each time a picking operation is performed. Inthis way, a known quantity of beads may be captured and transferred in arepeatable and efficient manner.

[0034] Syringe pump 30 is operated for a time sufficient to allow thebeads to be captured within lumen 20. After a certain time period,operation of syringe pump 30 is ceased and capillary tube 14 is removedfrom reservoir 48. Capillary tube assembly 12 is then moved over plate52 until capillary tube 14 is aligned with a desired well 54. Syringepump 30 is then operated to force liquid through line 32 to expel thecaptured beads into the aligned well. Capillary tube assembly 12 maythen be moved over reservoir 48 and the process repeated to transferbeads 26 into the desired number of wells. Plate 52 is then ready forappropriate biological screening or other processing as is known in theart.

[0035] In some cases, it may be desirable to increase the number ofcapillary tubes in order to increase the number of beads that may betransferred during a single picking operation. One system 56 thatincludes such features is illustrated in FIG. 2. System 56 comprises acapillary tube manifold assembly 58 which includes an array of capillarytube assemblies that may be constructed in a manner similar to thatpreviously described in connection with FIG. 1. Hence, for convenienceof discussion, the capillary tube assemblies will be described using thesame reference numerals used in describing capillary tube assembly 12 ofFIG. 1. For convenience of illustration, capillary tube manifoldassembly 58 is shown in greater detail in FIG. 3.

[0036] Fluidly connecting each capillary tube assembly 12 is a fluidmanifold 60. As shown, assembly 58 includes eight capillary tubes 14.Further, eight fluid delivery lines 62 are coupled to manifold 60. Fluidlines 62 are in turn coupled to a syringe pump 64. However, it willappreciated that other numbers of capillary tubes may be incorporatedinto manifold assembly 58. Further, although a separate fluid deliveryline is provided for each capillary tube 14, it will be appreciated thatmanifold 60 may be configured to evenly distribute fluids or providesuction to each capillary tube 14 so that only one fluid delivery linewould be needed. In such a case, syringe pump 64 may be configured to beessentially identical to syringe pump 30 of FIG. 1.

[0037] Syringe pump 64 comprises a housing 66 that includes multiplesyringe mechanisms 68 that may be similar to syringe mechanism 36 ofFIG. 1. Valve structures 70 are also provided to permit coupling ofsyringe mechanism 68 to fluid delivery lines 62. Also coupled to valvestructure 70 are fluid delivery lines 72 that terminate at a manifold 74which receives liquid from a liquid supply 76 via a line 78.

[0038] With such a configuration, syringe pump 64 may be operated tofill syringe mechanism 68 with liquid from supply 76. Syringe pump 64may then be operated to prime lines 62 and to aspirate liquids intocapillary tubes 14 to capture beads within capillary tubes 14 in amanner similar to that previously described in connection with FIG. 1.

[0039] System 56 further includes a movable stage 80 which is movablealong X and Y axes as indicated by the arrows. Positioned on stage 80 isa multi-well plate 82 having a plurality of wells 84 as is known in theart. Also held on stage 80 is a plate 86 having a plurality ofreservoirs 88 that each include multiple solid supports. Conveniently,reservoirs 88 may include beads which originated from the same or from adifferent synthesis pool/library. Use of reservoirs 88 is advantageousin that the beads may be stored within plate 86 without experiencingcross-contamination. Although not shown, a mechanism is also provided totranslate manifold assembly 58 along the Z axis to permit capillarytubes 12 to be moved into reservoirs 88 and into wells 84 as describedhereinafter. Conveniently, a controller 90 is provided to controlmovement of stage 80, movement of the mechanism to move manifoldassembly 50 and to control operation of syringe pump 64. In this way,the transfer of beads may occur in a fully automated manner.

[0040] For example, one method of operation for transferring beads fromreservoirs 88 to wells 84 is by using controller 90 to operate syringepump 64 to fill syringe mechanisms 68 with liquid from supply 76 aspreviously described. Controller 90 may then send a signal to syringepump 64 to prime lines 62 and lumens 20. Controller 90 may then send asignal to stage 80 to align reservoirs 88 with capillary tubes 14 and tomove manifold assembly 58 downward until capillary tubes 14 are withinreservoirs 88.

[0041] Once capillary tubes 14 are within reservoirs 88, controller 90may be operated to further prime the lines and to expel any liquid inorder to compensate for the liquid to be aspirated when sucking thebeads within capillary tubes 14. Controller 90 then sends a signal tosyringe pump 64 to aspirate liquids into capillary tubes 14 for a timesufficient to capture the desired number of beads into each of capillarytubes 14. As with system 10 of FIG. 1, the number of captured beads maybe controlled simply by controlling the length of wire 22 within lumen20. After the specified time has elapsed, controller 90 sends a signalto remove capillary tubes 14 from reservoirs 88. Stage 80 is then movedto align capillary tubes 14 with a desired row of wells in plate 82.Manifold assembly 58 is then moved downward and controller 90 sends asignal to syringe pump 64 to irrigate liquids through capillary tubes 14in order to expel the captured beads into the aligned wells 84 of plate82. This process may be repeated as many times as desired in order tofill each of wells 84 of plate 82. Plate 82 may then be used in abiological screening or other process as is known in the art.

[0042] System 56 may also be used to transfer beads from one multiwellplate to another. For example, if one of wells 84 produced a positiveresult during the screening process, system 56 may be employed toindividually remove the beads from that well and to place them into thewells of another multiwell plate so that further screening may occur toidentify the compound synthesized onto the bead.

[0043] Referring now to FIGS. 4 and 5, one embodiment of a capillarytube of manifold assembly 92 will be described. Assembly 92 comprises ahousing 94 to which are coupled a plurality of wire adjustmentmechanisms 96 and a plurality of capillary tube assemblies 98. Housing94 includes a plurality of ports 100 to permit manifold assembly 92 tobe coupled to a syringe pump in a manner similar to that described withprevious embodiments. As best shown in FIG. 6, housing 94 furtherincludes a plurality of openings 102 into which wire adjustmentmechanisms 96 may be inserted. Housing 94 further includes openings 104for receiving capillary tube assemblies 98.

[0044] As best shown in FIGS. 5A and 6, wire adjustment mechanism 96comprises a female/male adapter 106 that is insertable into opening 102.Insertable into adapter 106 is a sleeve 108 through which a wire 110 isinserted. Merely by way of example, female/male adapted 106 may beconstructed of a stainless steel 10-32 to 114-28 adapter, commerciallyavailable from Upchurch Scientific. Sleeve 108 may be constructed of aPEEK tubing sleeve, 0.008 inch OD, 1.25 inch long, commerciallyavailable from Upchurch Scientific. Wire 110 may be obtained fromCalifornia Fine Wire Company. Positioning of wire 110 through sleeve 108is shown in greater detail in FIG. 5C. Sleeve 108 is configured suchthat wire 110 may slide through sleeve 108 to adjust the distance withwhich wire 110 extends into capillary tube assembly 98. The connectionbetween sleeve 108 and wire 110 is also configured to provide asufficient seal so that liquids introduced into or withdrawn from port100 will not leak through sleeve 108. Further, the connection betweensleeve 108 and adaptor 106 are configured to prevent any fluid leakage.

[0045] Capillary tube assembly 98 comprises a female/male adaptor 112that is insertable into opening 104 of housing 94. Adaptor 112 isemployed to couple a sleeve 114 to housing 94. Inserted into sleeve 114is a length of tubing 116. Movably received within tubing 116 is wire110.

[0046] Hence, by grasping wire 110 where it exits sleeve 108, a user mayadjust the distance between a distal end 118 of wire 10 and a distal end120 of tubing 116. This distance, in turn, defines a space where thebeads will be captured. Hence, the number of beads that may be capturedinto tubing 116 may be adjusted simply by adjusting the location of wire110 within tubing 116. Conveniently, the adjustment of wire 110 mayoccur manually or with the use of automated equipment.

[0047] The connection between sleeve 114 and tubing 116, as well as theconnection between sleeve 114 and adapter 112, are sufficiently tight toprevent any fluid leakage. However, the spacing between wire 110 andtubing 116 is sufficient to permit the passage of fluids, such as whenproviding a vacuum for the bead picking process or positive pressure forfluid delivery or bead dispensing.

[0048] It will be appreciated that manifold assembly 92 may beconstructed of a variety of material and to have a variety of sizes.Merely by way of example, housing 94 may be constructed ofpolypropylene, stainless steel, Teflon, or the like. Tubing 116 may beconstructed of a polyimide capillary tube and may have, for example, a198 μm inner diameter and a 236 μm outer diameter. Wire 110 may beconstructed of tungsten and have a diameter of about 127 μm. Suchdimensions are particularly useful with beads having a diameter in therange from about 120 μm to about 140 μm. However, it will be appreciatedthat the dimensions of manifold assembly 92 may be varied depending onthe particular size of bead, the fluids involved, and the like.

[0049] Hence, in a bead picking operation, length of tubing 116 may beinserted into reservoirs having a plurality of beads. Fluids may then beaspirated through port 100 which causes a suction force to be created atdistal end 112 of tubing 116. As such, one or more beads will be drawninto tubing 16 depending upon the positioning of wire 110 within tubing116. Once the beads have been captured, manifold assembly 92 may bemoved to another location and fluid under positive pressure introducedinto port 110 to cause fluid to be irrigated out of tubing 116 to expelthe captured beads.

[0050] Referring now to FIG. 7, one method for transferring beads aspart of a biological screening process will be described. The processbegins at step 122 where tubular member is placed into a reservoirhaving beads with the synthesized chemicals. A known number of beads isthen aspirated into the tubular member as illustrated in step 124. Thetubular member is then removed from the reservoir and placed over a wellof a multiwell plate as shown in step 126. Positive pressure isintroduced into the tubular member to expel the beads into one of thewells as illustrated in step 128. If more wells are to receive beads,the process reverts back to step 122 as illustrated in step 130. If allof the desired wells are filled with beads, the process proceeds to step132 where the beads within the wells may be biologically screenedaccording to processes known in the art. The wells are then evaluatedfor any positive outcomes as illustrated in step 134. If no positiveoutcomes are identified, the process ends at step 136. If one or morewells are identified, the process proceeds to step 138 and the tubularmember may be introduced into the well to remove one or more of thebeads. The bead may then be transferred to another well as illustratedin step 140. This process is repeated as many times as necessary inorder to remove all of the beads as illustrated in step 142. Optionally,as shown in step 144, the transferred beads may be further screened asshown in step 144 to identify the compounds on the beads.

[0051] The invention has now been described in detail for purposes ofclarity of understanding. However, it will be appreciated that certainchanges and modifications may be practiced within the scope of theappended claims.

What is claimed is:
 1. A system for processing a plurality of solidsupports, the system comprising: a tubular member having a proximal end,a distal end, and a lumen terminating at the distal end; a stoppositioned within the lumen at a location spaced above the distal end,wherein the stop is sized to permit fluids to pass through the lumenwhile preventing passage of solid supports; and a fluid transfer devicethat is configured to transfer fluids through the lumen such that when afluid containing one or more solid supports is aspirated into the lumen,a solid support may be drawn into the lumen to lodge against the stop.2. A system as in claim 1, wherein the fluid transfer device is furtherconfigured to force liquids out of the distal end to expel any solidsupports within the lumen.
 3. A system as in claim 2, wherein the fluidtransfer device comprises a syringe pump and a length of tubing couplingthe syringe pump to the tubular member, wherein the syringe pump isoperable to aspirate fluids into the tubular member to capture one ormore solid supports into the lumen and to irrigate fluids from thetubular member to expel any captured solid supports.
 4. A system as inclaim 3, further comprising a source of fluid coupled to the syringepump.
 5. A system as in claim 1, wherein the stop comprises a wire thatis slidable within the lumen to permit the spacing between a distal endof the wire and the distal end of the tubular member to be adjustable.6. A system as in claim 1, further comprising a reservoir having aplurality of solid supports, and a moving mechanism to move the tubularmember relative to the reservoir to permit placement of the distal endof the tubular member into the reservoir.
 7. A system as in claim 6,further comprising a plate having a plurality of wells, and wherein themoving mechanism is configured to move the tubular member relative tothe plate to permit any solid supports to be expelled from the tubularmember and into at least one of the wells.
 8. A system as in claim 7,wherein the moving mechanism comprises a movable arm to move the tubularmember along the Z axis, and movable stage onto which the reservoir andthe plate are held, wherein the stage is movable along the X and Y axis.9. A system as in claim 6, further comprising a controller to controloperation of the fluid transfer device and the moving mechanism.
 10. Asystem as in claim 1, further comprising a plurality of tubular members,each having a lumen and a stop disposed in the lumen, and a manifoldcoupled to each of the tubular members, and wherein the fluid transferdevice is coupled to the manifold.
 11. A system as in claim 1, whereinthe lumen has a diameter in the range from about 190 μm to about 210 μm,and wherein the solid supports have a mean diameter in the range fromabout 120 μm to about 140 μm.
 12. A device for processing solid supportsthat are held within a fluid, the device comprising: a tubular memberhaving a proximal end, a distal end, and a lumen terminating at thedistal end, wherein the lumen has a diameter in the range from about 190μm to about 210 μm; a wire positioned within the lumen at a locationspaced above the distal end, wherein the wire has an outer diameter inthe range from about 125 μm to about 150 μm to permit fluids to passthrough the lumen while preventing passage of solid supports when fluidsare aspirated into the lumen from the distal end.
 13. A method forprocessing solid supports having at least one chemical synthesizedthereon, the method comprising: providing a tubular member having aproximal end, a distal end, and a lumen terminating at the distal end,and a stop that is positioned within the lumen at a location spacedabove the distal end; placing the distal end of the tubular member intoa fluid having a plurality of solid supports; and aspirating at leastsome of the fluid into the lumen and past the stop to draw at least oneof the solid supports into the lumen until lodging against the stop. 14.A method as in claim 13, further comprising aspirating additional fluidto draw into the lumen multiple solid supports in a linear array untilthe lumen is filled with solid supports between the stop and the distalend.
 15. A method as in claim 14, further comprising capturing 1 toabout 10 solid supports within the lumen.
 16. A method as in claim 13,further comprising removing the tubular member from the liquid, andforcing fluid through the lumen and past the stop to expel the solidsupport from the tubular member.
 17. A method as in claim 13, whereinthe fluid and the solid supports are held within a reservoir, andfurther comprising moving the tubular member relative to the reservoirto place the distal end into the fluid.
 18. A method as in claim 17,further comprising removing the tubular member from the reservoir,positioning the tubular member over a multiwell plate, and expelling thesolid support into a well of the multiwell plate.
 19. A method as inclaim 13, wherein the lumen has a diameter in the range from about 190μm to about 210, and wherein the solid supports have a mean diameter inthe range from about 120 μm to about 140 μm.
 20. A method as in claim13, further comprising priming the lumen with a fluid to removesubstantially all gas bubbles from the lumen prior to aspirating thefluid.
 21. A method as in claim 13, further comprising providingmultiple tubular members that each have a lumen and a stop within thelumen, and placing a distal end of each of the tubular memberssimultaneously into the fluid, and aspirating fluid into each of thelumens to draw at least one solid support into each of the lumens.